NUROFEN DAY & NIGHT COLD & FLU

For short-term use only. 4). The patient should consult a doctor if symptoms persist or worsen, or if the product is required for more than 10 days.

Adults, the elderly and children over 12 years:

Two tablets up to 3 times a day. Leave at least four hours between doses and do not take more than 6 tablets in any 24hour period. Not to be given to children under 12 years. Method of administration For oral administration.

The following list of adverse effects relates to those experienced with ibuprofen at OTC doses (maximum 1200 mg ibuprofen per day) and phenylephrine hydrochloride, in short-term use. In the treatment of chronic conditions, under long-term treatment, additional adverse events may occur.

Adverse events which have been associated with ibuprofen and phenylephrine hydrochloride are given below, tabulated by system organ class and frequency.

Frequencies are defined as:

Very common (≥1/10); Common (≥1/100 and <1/10); Uncommon (≥1/1000 and <1/100); Rare (≥1/10,000 and <1/1000); Very rare (< 1/10,000); Not known (cannot be estimated from the available data). Within each frequency grouping, adverse events are presented in order of decreasing seriousness.

System Organ Class Frequency Adverse Events Blood and Lymphatic System Disorders Very rare Haematopoietic disorders1 Uncommon Hypersensitivity with urticaria and pruritus2 Immune System Disorders Very rare Severe hypersensitivity reactions, including facial, tongue and throat swelling, dyspnoea, tachycardia, and hypotension (anaphylaxis, angioedema or severe shock) 2 Uncommon HeadacheNervous System Disorders Very rare Aseptic meningitis3 Cardiac Disorders Not known Not known Cardiac failure, oedema4, palpitations Kounis syndrome Vascular Disorders Not known Hypertension4 Respiratory, Thoracic and Mediastinal Disorders Not known Respiratory tract reactivity comprising exacerbation of asthma, bronchospasm or dyspnoea2 Uncommon Abdominal pain, nausea and dyspepsia5 Gastrointestinal Disorders Rare Diarrhoea, flatulence, constipation and System Organ Class Frequency Adverse Events vomiting Very rare Peptic ulcer, gastrointestinal perforation or gastrointestinal haemorrhage, melaena, haematemesis6.

Mouth ulceration, gastritis Not known Exacerbation of colitis and Crohn's disease7 Hepatobiliary Disorders Very rare Liver disorder Uncommon Skin rash2 Very rare Severe cutaneous adverse reactions (SCARs) (including Erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis)2 Skin and Subcutaneous Tissue Disorders Not known Drug reaction with eosinophilia and systemic symptoms (DRESS syndrome) Acute generalised exanthematous pustulosis (AGEP) Photosensitivity reactions Metabolism and Nutrition Disorders Not known Not known Decreased Appetite Hypokalaemia* (The reference numbers for the description of the selected Adverse reaction should be updated throughout the table) Very rare Acute renal failure8 Not known Urinary retention Not known Ureteric colic, dysuria Renal and Urinary Disorders Not known Renal tubular acidosis* Investigations Very rare Haemoglobin decreased Description of Selected Adverse Reactions 1 Examples include anaemia, leucopenia, thrombocytopenia, pancytopenia and agranulocytosis.

First signs are fever, sore throat, superficial mouth ulcers, flu-like symptoms, severe exhaustion, unexplained bleeding and bruising. 2 Hypersensitivity reactions have been reported following treatment with ibuprofen and these may consist of: (a) Non-specific allergic reaction and anaphylaxis.

g. asthma, aggravated asthma, bronchospasm or dyspnoea. g. pruritus, urticaria, angioedema and, more rarely, exfoliative and bullous dermatoses (including epidermal necrolysis and erythema multiforme). 3 The pathogenic mechanism of drug-Induced aseptic meningitis is not fully understood.

However, the available data on NSAID-related aseptic meningitis points to a hypersensitivity reaction (due to a temporal relationship with drug intake, and disappearance of symptoms after drug discontinuation). Of note, single cases of symptoms of aseptic meningitis (such as stiff neck, headache, nausea, vomiting, fever or disorientation) have been observed during treatment with Ibuprofen in patients with existing auto-immune disorders (such as systemic lupus erythematosus and mixed connective tissue disease).

4). 5 The most commonly-observed adverse events are gastrointestinal in nature. 6 Sometimes fatal, particularly in the elderly. 4. 8 Especially in long-term use, associated with increased serum urea and oedema. Also includes papillary necrosis.

*Renal tubular acidosis and hypokalaemia have been reported in the post-marketing setting typically following prolonged use of the ibuprofen component at higher than recommended doses Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.

It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

Ibuprofen Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms (see gastrointestinal and cardiovascular risks below). The elderly are at increased risk of consequence of adverse reactions to NSAIDs, especially gastrointestinal bleeding and perforation which may be fatal.

Respiratory:

Bronchospasm may be precipitated in patients suffering from or with a previous history of bronchial asthma or allergic disease. 5). 8). 8). Renal tubular acidosis and hypokalaemia may occur following acute overdose and in patients taking ibuprofen products over long periods at high doses (typically greater than 4 weeks), including doses exceeding the recommended daily dose.

8).

Cardiovascular and cerebrovascular effects:

Cases of Kounis syndrome have been reported in patients treated with Nurofen Day & Night Cold & Flu 200mg/5mg Tablets. Kounis syndrome has been defined as cardiovascular symptoms secondary to an allergic or hypersensitive reaction associated with constriction of coronary arteries and potentially leading to myocardial infarction.

Caution (discussion with doctor or pharmacist) is required prior to starting treatment in patients with a history of hypertension and/or heart failure as fluid retention, hypertension and oedema have been reported in association with NSAID therapy.

Clinical studies suggest that use of ibuprofen, particularly at a high dose (2400 mg/day) may be associated with a small increased risk of arterial thrombotic events (for example, myocardial infarction or stroke). Overall, epidemiological studies do not suggest that low dose ibuprofen (≤1200 mg/day) is associated with an increased risk of arterial thrombotic events.

Patients with uncontrolled hypertension, congestive heart failure (NYHA II-III), established ischaemic heart disease, peripheral arterial disease, and/or cerebrovascular disease should only be treated with ibuprofen after careful consideration and high doses (2400 mg/day) should be avoided.

g. hypertension, hyperlipidaemia, diabetes mellitus, smoking), particularly if high doses of ibuprofen (2400 mg/day) are required.

Impaired female fertility:

There is limited evidence that drugs which inhibit cyclo- oxygenase/prostaglandin synthesis may cause impairment of female fertility by an effect on ovulation. This is reversible on withdrawal of treatment. 8). GI bleeding, ulceration or perforation, which can be fatal, has been reported with all NSAIDs at any time during treatment, with or without warning symptoms or a previous history of serious GI events.

3), and in the elderly. These patients should commence treatment on the lowest dose available. Patients with a history of GI toxicity, particularly the elderly, should report any unusual abdominal symptoms (especially GI bleeding), particularly in the initial stages of treatment.

5). When GI bleeding or ulceration occurs in patients receiving ibuprofen, the treatment should be withdrawn. 8). Most of these reactions occurred within the first month. If signs and symptoms suggestive of these reactions appear ibuprofen should be withdrawn immediately and an alternative treatment considered (as appropriate).

Masking of symptoms of underlying infections This medicinal product can mask symptoms of infection, which may lead to delayed initiation of appropriate treatment and thereby worsening the outcome of the infection. This has been observed in bacterial community acquired pneumonia and bacterial complications to varicella.

When this medicine is administered for fever or pain relief in relation to infection, monitoring of infection is advised. In non-hospital settings, the patient should consult a doctor if symptoms persist or worsen.

The label will include:

Read the enclosed leaflet before taking this product. Do not take if you: • Have (or have had two or more episodes of) a stomach ulcer, perforation or bleeding. • Are allergic to ibuprofen or any other ingredient of the product, aspirin or other related painkillers.

• Are taking other NSAID painkillers, or aspirin with a daily dose above 75 mg. • Are in the last 3 months of pregnancy Speak to a pharmacist or your doctor before taking if you: • […]

1. g. asthma, rhinitis, angioedema or urticaria) in response to ibuprofen, acetylsalicylic acid (aspirin), or other non- steroidal anti-inflammatory drugs (NSAIDs). Active or history of recurrent peptic ulcer/haemorrhage (two or more distinct episodes or proven ulceration or bleeding).

History of gastrointestinal bleeding or perforation, related to previous NSAIDs therapy. 4). 4). 6). 5). Hyperthyroidism. Contraindicated in patients currently receiving or within two weeks of stopping therapy with monoamine oxidase inhibitors (MAOIs).

Avoid in patients with prostatic enlargement.

Phaeochromocytoma:

Phenylephrine should not be used in patients with phaeochromocytoma.